This invention relates to a method and apparatus for determining oxygen partial pressure (PO.sub.2) and temperature simultaneously in living tissue at multiple sites of the tissue. particularly, this invention relates to such an apparatus which can also determine thermal conductivity, thermal diffusivity, SAR (Specific Absorption Rate) and blood perfusion in the living tissue at multiple sites.
Interest in the fundamental mechanisms of heat transfer in living tissue and in accurate clinical thermometry derives from the fact that many patients with malignancies who failed surgery, radiation and/or chemotherapy are responsive to the local application of heat resulting in elevated tumor temperatures. Well-managed clinical application of hyperthermia requires the ability to produce specific, well-characterized temperature elevations in precisely selected volumes of tissue that comprise the malignancy. The corresponding engineering requirement is the ability to control the temporal and spatial characteristics of the absorbed thermal dose so as to produce the desired temperature distribution for the specific malignanc being treated.
The achievement and accurate measurement of the elevated temperature distribution is thus of primary importance in any hyperthermia system. The existence of computerized axial tomography makes three-dimensional visualization of tissue densities possible, and contrast angiography can also be used to map the vasculature in the tissue volume. However, neither produces temperature or oxygen images. In terms of hyperthermia heating means, microwave, radio-frequency currents and ultrasound have been used as non-invasive sources of volumetric heat generation in tissue. Each of these three heat source means has specific advantages and limitations. An ideal system would provide control of the temporal and spatial characteristics of the heat source in order to shape the volumetric power deposition pattern to the specific requirements of the tumor mass.
In view of the rather significant tissue temperature gradients that can exist as a consequence of differential blood flow and thermal conductivity (both of which are enhanced with increased perfusion in surrounding tissue) and the clear evidence that even a small difference in temperature level could be crucial to the success of hyperthermia, it is equally crucial that good thermometry be available. Since the temperature gradient will be largest at boundaries of differential energy absorption, perfusion and/or conductivity, it is important that the temperature at the tumor margin or proliferating edge be known. It could well be that the apparent resistance of some tumor peripheries to hyperthermia is really due to inadvertent sublethal heating due to lack of adequate thermometry at the tumor boundaries. It is the lowest temperature in the tumor and the highest temperature in the normal tissue that is limiting in the management of tumors by hyperthermia.
The state of tissue perfusion is a primary factor in local transport of heat, the regulation of which is clearly crucial for hyperthermia; of drugs, the delivery of which is crucial in chemotherapy; and of oxygen and nutrients which are known to be important for effective radiation therapy. Thus, optimization of each of these individual cancer therapies (or synergism through combined use) each requires knowledge of the distribution and magnitude of the local level of perfusion. Differences in perfusion rates between the core and periphery of rapidly growing tumors have been found using a number of techniques, including the embedded thermistor probe (Holmes et al., ASME Advances in Bioengineering, pp. 147-149,1979). Because blood flow is known to have a dramatic influence on the temperature distribution in tissue during hyperthermia, knowledge of the magnitude and the distribution of perfusion in both the tumor and surrounding host tissue is necessary for accurate thermal therapy planning and for directing the local deposition of heat to produce uniform temperature elevations over the desired region.
There also appear to be a few important difference between blood flow in tumor and normal tissue which include: the character and distribution of the vasculature, as well as the ability to increase local perfusion in response to thermal stress at various levels and durations of local hyperthermia. Normal tissue such as skin can increase blood supply as much as seven times in response to elevated temperatures of 42-43.degree. C. This responsive cooling mechanism has been observed as reductions in measured temperatures during hyperthermia and must be taken into account when calculating local power requirements.
Copending U.S. patent application Ser. No. 730, 614, now U.S. Pat. No. 4,741,343, discloses a probe adapted to measure oxygen partial pressure and temperature in body tissue. The probe utilizes discreet thermistors for measuring temperature which requires individual placement of the thermistors on the probe substrate thereby complicating the fabrication process. In addition, this probe does not permit a four point measurement process so that the measurements obtained are undesirably dependent upon the resistance of the leads to the thermistors. In addition, the thermistors protrude from the probe surface thereby increasing the possibility that they will be damaged when the probe is inserted into tissue. Because of the discrete thermistor construction, which makes substantial amounts of gold, the thermal conductivity of the thermistor probe does not match tissue. This will create disturbances in the thermal gradients of interest.
It would be desirable to monitor temperature distributions accurately during hyperthermic treatments of cancer while minimally perturbing the local thermal environment. Furthermore, it would be desirable to provide a means for obtaining these measurements at a plurality of tissue locations as well as other measurements of tissue characteristics including blood perfusion, thermal conductivity and thermal diffusivity.
In addition, determination of the spatial distribution of PO.sub.2 in ionizing radiation therapy of tumors is important. Regions of tumors with low PO.sub.2 do not respond adequately to ionizing radiation therapy. Therefore, direct assessment of the spatial distribution of PO.sub.2 in tumors is useful in establishing whether or not radiation therapy will be successful or whether or combined radiation/hyperthermia therapy will be needed. In order to be accurate, PO.sub.2 measurements at multiple sites must each be temperature compensated, thereby requiring a temperature measurement at each site.